Functional analysis of the role of MyD88 in multiple myeloma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K22819
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Sapporo Medical University
• Principal Investigator: Nakamura Hajime 札幌医科大学, 医学部, 研究員 (10792666)
• Project Period (FY): 2020-09-11 – 2023-03-31
• Keywords: 多発性骨髄腫 / ST2825 / MyD88

Outline of Final Research Achievements

Myeloid differentiation factor 88 (MyD88), which is a key regulator of nuclear factor kappa B (NF-κB), plays an important role in tumorigenesis in lymphoid malignancies such as Waldenstrom’s macroglobulinemia (WM). However, its biological function in multiple myeloma (MM), which is a malignant plasma cell disorder like WM, remains unexplored.
We first demonstrated that higher expression MyD88 was significantly correlated with poor survival in patients with MM. Interestingly, bioinformatic analysis also revealed that MyD88 gene alteration, which is recognized in nearly 80% of patients with WM, was extremely rare in MM. In addition, ST2825 suppressed cell growth followed by apoptosis. Furthermore, ST2825 induced intracellular reactive oxygen species (ROS) in MM cells, and N-acetyl-L-cysteine, which is known as a ROS scavenger, significantly decreased the number of apoptotic MM cells evoked by ST2825 treatment. In summary, this study provides novel treatment strategies to conquer MM.

Free Research Field

臨床腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究ではこれまで報告のないMMにおけるMyD88の機能解析を行い、細胞増殖や転移浸潤に及ぼす影響を明らかにし、最終的に新規のMM治療戦略の開発を目指した。その結果として、MyD88及びその阻害剤であるST2825がMMの新規治療戦略に繋がる可能性を示した。様々な新規治療薬の開発を以てしても未だ治癒の難しい再発難治性MM患者の予後改善に寄与することが期待され、将来的にその他の癌腫への応用も考慮され、本研究が社会へ波及する効果は大きいと考えられた。